1. Field of the Invention
The present invention relates to tricyclic benzazepine compounds having antiallergic activity and pharmaceutical compositions, useful for treatment and prevention of allergic diseases, comprising at least one of the tricyclic benzazepine compounds as an active ingredient. The present invention relates also to intermediate for providing the above compounds and pharmaceutical compositions and a process for producing the same.
2. Background Art
In recent years, allergic reactions induced by various stimuli, such as immunoreactions, have been clarified to be divided into two reactions, i.e., an immediate phase response which occurs immediately after the stimulation and a late phase response which occurs several hours after the stimulation (see, for example, "Late Asthmatic Responses", P. M. O'byrne, J. Dolovich and F. E. Hargreave, Am. Rev. Respir. Dis., 1987; 136: 740-751). Especially, importance has been attached to the control of the latter reaction.
In clinical studies, there are few drugs satisfactorily useful for the late phase allergic response, and the development of drugs having therapeutic effect for both the immediate phase response and the late phase response has been expected in the art.
Sodium cromoglicate are known as a representative drug for inhibiting the immediate and late phase allergic responses. This drug is clinically administered by inhalation because of its poor oral absorption. The administration by inhalation, however, is disadvantageous in that it is difficult to properly administer the drug to babies, infants, and children and, in addition, it is difficult to continuously administer the drug to patients having high sensitivity to inhalation stimuli.
For the above reason, the development of drugs, which can inhibit both the immediate and late phase responses, can be orally administered, and have excellent efficacy, have been desired in the art.
Further, in recent years, many studies on antiallergic agents and therapeutic agents for asthma have been advanced in the art. Among them, tricyclic compounds including heptacyclic compounds have been reported. Examples thereof include dibenzoxepine derivatives (Japanese Patent Laid-Open Nos. 10784/1988 and 78292/1993 and Chemical & Pharmaceutical Bulletin, vol. 39, No. 10, 2724-2728 and 2729-2733 (1991)), dibenzoxazepine derivatives (Japanese Patent Laid-Open Nos. 184963/1991, 211071/1992, and 65257/1993 and European Patent No. 5180720), and dibenzocycloheptene derivatives (International Patent WO/93-13068).
Compounds containing a hetero ring have also been reported as the antiallergic agent, and examples thereof include dibenzoxepinopyridine derivatives (European Patent No. 515158), benzocycloheptathiophene derivatives (Japanese Patent Laid-Open Nos. 294277/1991 and 226916/1992), benzocycloheptapyridine derivatives (Japanese Patent Laid-Open No. 59040/1993), triazolobenzoxepine derivatives (Journal of Chemical Research(s), 400-401 (1984)), and thieno- (pyrazolo-, thiazolo-)benzothiazepine derivatives (European Patent No. 547705).
Some of them have central or circulatory side effects and have problems of dissociation of the antiallergic action from central action, such as sedation, antidepression, or antianxiety, or circulatory action, such as vasodepression or anti-thrombogenic action. Among compounds having structures similar thereto, only few compounds, such as cyproheptadine hydrochloride, have been put as antiallergic agents on the market.
For other analogous compounds, for example, pyridobenzoxazepine derivatives have been reported as an HIV-1 reverse transcriptase inhibitor (Japanese Patent Laid-Open No. 178390/1992), triazolobenzoxazepine derivatives as an antidepressant (Journal of Heterocyclic Chemistry, vol. 22, 1693-1701 (1985)), and triazolobenzdiazepine derivatives as an antipsychotic agent (Journal of Medicinal Chemistry, vol. 32, No. 10, 2375-2381 (1989)).
As described above, the development of drugs, which can inhibit both the immediate and late phase allergic responses, can be orally administered, and have excellent efficacy, have been desired in the art.
The present inventors have previously reported, as such compounds, tricyclic benzazepine compounds containing a triazole ring (International Publication WO 95/18130).